Abstract

Use of the BioBreeding (BB) rat to model human insulin‐dependent diabetes mellitus (IDDM) is useful in that characteristics
of diabetes in the BB rat closely parallel those observed in human IDDM. Diabetic animals can be biopsied, autopsied, and
bred to study the genetic basis of IDDM. The genetic, immunological, and environmental components of the disease can all be
investigated under controlled conditions. Two inbred lines of BB have been used in the majority of published studies using
this model system; these rats are designated as diabetes prone (DP‐BB/Wor) and diabetes resistant (DR‐BB/Wor). This unit presents
two protocols for the diagnosis and prevention of spontaneous IDDM in DP‐BB/Wor rats. Two alternate protocols are given for
the induction of autoimmune disease in DR‐BB/Wor rats and for the adoptive transfer of autoimmunity into histocompatible athymic
WAG
nu/nu recipient rats. Support protocols are also given for diagnosis of insulitis, treatment of diabetic rats with insulin, and
serological analysis of blood samples from sentinel rats to monitor the pathogen status of the colony.

NOTE: All materials taken into SPF or VAF animal rooms should be vacuum autoclaved, if possible. Nonautoclavable materials and
the exposed surfaces of tubes, equipment, and other objects should be disinfected by spraying with Clidox disinfecting solution.
Personnel handling the animals should wear sterile gowns or scrub suits, bonnets, masks, gloves, and shoe covers.

Alternate Protocol 1: Induction of IDDM in Diabetes‐Resistant BB Rats

Hybridoma DS4.23 cells (available from the Division of Diabetes, University of Massachusetts Medical School, Worcester, Mass.)

NOTE: All solutions and equipment coming into contact with cells should be sterile, and proper sterile technique should be used
accordingly. Injections should be performed in a laminar flow hood in the animal room, with as much adherence to sterile technique
as possible.

Basic Protocol 2: Prevention of IDDM in Diabetes‐Prone BB Rats

Materials

21‐ to 30‐day old DP‐BB rats of either sex (available from Dennis Guberski; see )

8‐ to 12‐week old DR‐BB rats of either sex (available from Dennis Guberski)

NOTE: All solutions and equipment coming into contact with cells should be sterile, and proper sterile technique should be used
accordingly. Injections should be performed in a laminar flow hood in the animal room, with as much adherence to sterile technique
as possible.